History

Those affected by osteosarcoma often describe symptoms that begin weeks, months, or occasionally longer before being diagnosed. The most common presenting symptom is pain, particularly with activity. Patients often describe symptoms that suggest a sprain, arthritis, or "growing pains." They often identify a history of trauma as a trigger when the pains begin, although pathologic fractures are not particularly common (the exception being the telangiectatic subtype of osteosarcoma, which is commonly associated with pathologic fractures). If pain affects a lower extremity, patients often walk with a limp.

The lesion may cause swelling, depending on the size and location. Systemic symptoms, such as fever and night sweats, are rare. While 15-20% of patients initially present with lung metastasis, these rarely cause respiratory symptoms. Breathing symptoms usually indicate extensive lung involvement. Metastases to other sites are extremely rare, making other symptoms uncommon.

Osteosarcoma most commonly involves the distal femur and proximal tibia, followed by the proximal humerus and mid and proximal femur. As many as 20% of patients present with tumors of the flat bones of the body including the skull and pelvis. Tumors of the jaw are relatively uncommon.

Physical Examination

Physical findings are usually limited to those of the primary tumor site.

Mass: A palpable mass may be present. The mass may be tender and warm, although these signs are indistinguishable from those of osteomyelitis. Increased skin vascularity over the mass may be discernible. Pulsations or a bruit may be detectable.
Decreased range of motion: Joint involvement should be obvious on physical examination.
Lymphadenopathy: Involvement of local or regional lymph nodes is unusual.
Respiratory findings: Auscultation is usually uninformative unless extensive pulmonary disease is present.

Differential Diagnoses

Ries LAG, Smith MA, Gurney JG, et al. Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. NIH publication No. 99-4649. Bethesda, Md. National Institutes of Health;. 1999. [Full Text].
Longhi A, Pasini A, Cicognani A, et al. Height as a risk factor for osteosarcoma. J Pediatr Hematol Oncol. 2005 Jun. 27(6):314-8. [QxMD MEDLINE Link].
Pasic I, Shlien A, Durbin AD, et al. Recurrent focal copy-number changes and loss of heterozygosity implicate two noncoding RNAs and one tumor suppressor gene at chromosome 3q13.31 in osteosarcoma. Cancer Res. 2010 Jan 1. 70(1):160-71. [QxMD MEDLINE Link].
Wang Z, Cai H, Lin L, Tang M, Cai H. Upregulated expression of microRNA-214 is linked to tumor progression and adverse prognosis in pediatric osteosarcoma. Pediatr Blood Cancer. 2013 Sep 9. [QxMD MEDLINE Link].
He J, Wang J, Wang D, Dai S, Yv T, Chen P, et al. Association analysis between genetic variants of MDM2 gene and osteosarcoma susceptibility in Chinese. Endocr J. 2013 Aug 9. [QxMD MEDLINE Link].
Gorlick R, Janeway K, Lessnick S, Randall RL, Marina N, COG Bone Tumor Committee. Children's Oncology Group's 2013 blueprint for research: bone tumors. Pediatr Blood Cancer. 2013 Jun. 60 (6):1009-15. [QxMD MEDLINE Link].
[Guideline] Casali PG, Bielack S, Abecassis N, et al. Bone sarcomas: ESMO-PaedCan-EURACAN Clinical Practice Guidelines for diagnosis, treatment and follow-up. Ann Oncol. 2018 Oct 1. 29 (Suppl 4):iv79-iv95. [QxMD MEDLINE Link].
Kager L, Zoubek A, Dominkus M, Lang S, Bodmer N, Jundt G, et al. Osteosarcoma in very young children: experience of the Cooperative Osteosarcoma Study Group. Cancer. 2010 Nov 15. 116(22):5316-24. [QxMD MEDLINE Link].
Grimer RJ, Bielack S, Flege S, et al. Periosteal osteosarcoma--a European review of outcome. Eur J Cancer. 2005 Dec. 41(18):2806-11. [QxMD MEDLINE Link].
Meyers PA, Schwartz CL, Krailo MD, et al. Osteosarcoma: the addition of muramyl tripeptide to chemotherapy improves overall survival--a report from the Children's Oncology Group. J Clin Oncol. 2008 Feb 1. 26(4):633-8. [QxMD MEDLINE Link].
Chou AJ, Kleinerman ES, Krailo MD, et al. Addition of muramyl tripeptide to chemotherapy for patients with newly diagnosed metastatic osteosarcoma: a report from the Children''s Oncology Group. Cancer. 2009 Nov 15. 115(22):5339-48. [QxMD MEDLINE Link]. [Full Text].
Bacci G, Briccoli A, Longhi A, Ferrari S, Mercuri M, Faggioli F, et al. Treatment and outcome of recurrent osteosarcoma: experience at Rizzoli in 235 patients initially treated with neoadjuvant chemotherapy. Acta Oncol. 2005. 44(7):748-55. [QxMD MEDLINE Link].
Nagarajan R, Kamruzzaman A, Ness KK, Marchese VG, Sklar C, Mertens A, et al. Twenty years of follow-up of survivors of childhood osteosarcoma: a report from the childhood cancer survivor study. Cancer. 2011 Feb 1. 117(3):625-34. [QxMD MEDLINE Link]. [Full Text].
Mulrooney DA, Ness KK, Huang S, Solovey A, Hebbel RP, Neaton JD, et al. Pilot study of vascular health in survivors of osteosarcoma. Pediatr Blood Cancer. 2013 Oct. 60(10):1703-8. [QxMD MEDLINE Link].
Stohr W, Langer T, Kremers A, et al. Cisplatin-induced ototoxicity in osteosarcoma patients: a report from the late effects surveillance system. Cancer Invest. 2005. 23(3):201-7. [QxMD MEDLINE Link].
Nagarajan R, Clohisy DR, Neglia JP, et al. Function and quality-of-life of survivors of pelvic and lower extremity osteosarcoma and Ewing's sarcoma: the Childhood Cancer Survivor Study. Br J Cancer. 2004 Nov 29. 91(11):1858-65. [QxMD MEDLINE Link].
Ottaviani G, Robert RS, Huh WW, Palla S, Jaffe N. Sociooccupational and physical outcomes more than 20 years after the diagnosis of osteosarcoma in children and adolescents: Limb salvage versus amputation. Cancer. 2013 Jul 31. [QxMD MEDLINE Link].
Bacci G, Longhi A, Ferrari S, et al. Prognostic significance of serum lactate dehydrogenase in osteosarcoma of the extremity: experience at Rizzoli on 1421 patients treated over the last 30 years. Tumori. 2004 Sep-Oct. 90(5):478-84. [QxMD MEDLINE Link].
Mialou V, Philip T, Kalifa C, et al. Metastatic osteosarcoma at diagnosis: prognostic factors and long-term outcome--the French pediatric experience. Cancer. 2005 Sep 1. 104(5):1100-9. [QxMD MEDLINE Link].
Ilhan IE, Vural G, Berberoglu S, Kapucuoglu N, Cila A, Eke S. Quantitative thallium-201 scintigraphy in childhood osteosarcoma: Comparison with technetuim-99m MDP and magnetic resonance imaging in the evaluation of chemotherapeutic response. Pediatr Hematol Oncol. 2005 Mar. 22(2):153-62. [QxMD MEDLINE Link].
McCarville MB, Christie R, Daw NC, Spunt SL, Kaste SC. PET/CT in the evaluation of childhood sarcomas. AJR Am J Roentgenol. 2005 Apr. 184(4):1293-304. [QxMD MEDLINE Link].
Volker T, Denecke T, Steffen I, et al. Positron emission tomorgraphy for staging of pediatric sarcoma patients: results of a prospective multicenter trial. J Clin Oncol. Dec 1 2007. 25(34):5435-41.
Hawkins DS, Conrad EU 3rd, Butrynski JE, Schuetze SM, Eary JF. [F-18]-fluorodeoxy-D-glucose-positron emission tomography response is associated with outcome for extremity osteosarcoma in children and young adults. Cancer. 2009 Aug 1. 115(15):3519-25. [QxMD MEDLINE Link]. [Full Text].
Pignatti G, Bacci G, Picci P, et al. Telangiectatic osteogenic sarcoma of the extremities. Results in 17 patients treated with neoadjuvant chemotherapy. Clin Orthop Relat Res. 1991 Sep. 99-106. [QxMD MEDLINE Link].
Saab R, Rao BN, Rodriguez-Galindo C, Billups CA, Fortenberry TN, Daw NC. Osteosarcoma of the pelvis in children and young adults: the St. Jude Children's Research Hospital experience. Cancer. 2005 Apr 1. 103(7):1468-74. [QxMD MEDLINE Link].
Briccoli A, Rocca M, Salone M, et al. Resection of recurrent pulmonary metastases in patients with osteosarcoma. Cancer. 2005 Oct 15. 104(8):1721-5. [QxMD MEDLINE Link].
Man TK, Chintagumpala M, Visvanathan J, et al. Expression profiles of osteosarcoma that can predict response to chemotherapy. Cancer Res. 2005 Sep 15. 65(18):8142-50. [QxMD MEDLINE Link].
Mikulic D, Ilic I, Cepulic M, et al. Tumor angiogenesis and outcome in osteosarcoma. Pediatr Hematol Oncol. 2004 Oct-Nov. 21(7):611-9. [QxMD MEDLINE Link].
Kreuter M, Bieker R, Bielack SS, et al. Prognostic relevance of increased angiogenesis in osteosarcoma. Clin Cancer Res. 2004 Dec 15. 10(24):8531-7. [QxMD MEDLINE Link].
Chan HS, Grogan TM, Haddad G, DeBoer G, Ling V. P-glycoprotein expression: critical determinant in the response to osteosarcoma chemotherapy. J Natl Cancer Inst. 1997 Nov 19. 89(22):1706-15. [QxMD MEDLINE Link].
Link MP, Goorin AM, Miser AW, et al. The effect of adjuvant chemotherapy on relapse-free survival in patients with osteosarcoma of the extremity. N Engl J Med. 1986 Jun 19. 314(25):1600-6. [QxMD MEDLINE Link].
Link MP, Goorin AM, Horowitz M, et al. Adjuvant chemotherapy of high-grade osteosarcoma of the extremity. Updated results of the Multi-Institutional Osteosarcoma Study. Clin Orthop Relat Res. 1991 Sep. 8-14. [QxMD MEDLINE Link].
DeLaney TF, Park L, Goldberg SI, et al. Radiotherapy for local control of osteosarcoma. Int J Radiat Oncol Biol Phys. 2005 Feb 1. 61(2):492-8. [QxMD MEDLINE Link].
DeLaney TF, Liebsch NJ, Pedlow FX, et al. Phase II study of high-dose photon/proton radiotherapy in the management of spine sarcomas. Int J Radiat Oncol Biol Phys. 2009 Jul 1. 74(3):732-9. [QxMD MEDLINE Link]. [Full Text].
Anderson PM, Wiseman GA, Dispenzieri A, et al. High-dose samarium-153 ethylene diamine tetramethylene phosphonate: low toxicity of skeletal irradiation in patients with osteosarcoma and bone metastases. J Clin Oncol. 2002 Jan 1. 20(1):189-96. [QxMD MEDLINE Link].
Kobys VL, Konovalenko VF, Repin? NV, Golovko TS, Gulak LO, Tarasova TO, et al. Treatment of large osteosarcoma in children: new approach. Exp Oncol. 2013 Jun. 35(2):105-8. [QxMD MEDLINE Link].
[Guideline] NCCN Clinical Practice Guidelines in Oncology. Bone cancer. Version 1.2020. National Comprehensive Cancer Network. Available at https://www.nccn.org/professionals/physician_gls/pdf/bone.pdf. 2019 Aug 12; Accessed: January 5, 2021.
Lewis IJ, Nooij MA, Whelan J, et al. Improvement in histologic response but not survival in osteosarcoma patients treated with intensified chemotherapy: a randomized phase III trial of the European Osteosarcoma Intergroup. J Natl Cancer Inst. 2007 Jan 17. 99(2):112-28. [QxMD MEDLINE Link].
Gralla RJ, Osoba D, Kris MG, et al. Recommendations for the use of antiemetics: evidence-based, clinical practice guidelines. American Society of Clinical Oncology. J Clin Oncol. 1999 Sep. 17(9):2971-94. [QxMD MEDLINE Link].
Nagarajan R, Clohisy D, Weigel B. New paradigms for therapy for osteosarcoma. Curr Oncol Rep. 2005 Nov. 7(6):410-4. [QxMD MEDLINE Link].
Paiva MG, Petrilli AS, Moises VA, Macedo CR, Tanaka C, Campos O. Cardioprotective effect of dexrazoxane during treatment with doxorubicin: a study using low-dose dobutamine stress echocardiography. Pediatr Blood Cancer. 2005 Dec. 45(7):902-8. [QxMD MEDLINE Link].
Bacci G, Mercuri M, Longhi A, et al. Grade of chemotherapy-induced necrosis as a predictor of local and systemic control in 881 patients with non-metastatic osteosarcoma of the extremities treated with neoadjuvant chemotherapy in a single institution. Eur J Cancer. 2005 Sep. 41(14):2079-85. [QxMD MEDLINE Link].
Deutsch M, Tersak JM. Radiotherapy for symptomatic metastases to bone in children. Am J Clin Oncol. 2004 Apr. 27(2):128-31. [QxMD MEDLINE Link].
Laverdiere C, Hoang BH, Yang R, et al. Messenger RNA expression levels of CXCR4 correlate with metastatic behavior and outcome in patients with osteosarcoma. Clin Cancer Res. 2005 Apr 1. 11(7):2561-7. [QxMD MEDLINE Link].
Minegishi Y, Saito M, Morio T, et al. Human tyrosine kinase 2 deficiency reveals its requisite roles in multiple cytokine signals involved in innate and acquired immunity. Immunity. 2006 Nov. 25(5):745-55. [QxMD MEDLINE Link].

Media Gallery

Lateral plain radiograph of the knee reveals an osteosarcoma of the distal femur. The lesion is mainly posterior, with disruption and elevation of the periosteum (Codman triangle), and extends beyond the bone into the soft tissue.
Anteroposterior plain radiograph of the same with distal femoral osteosarcoma as shown in image above. The osteolytic lesion is apparent on the right side of the image.
MRI of the same distal femoral osteosarcoma as in images shown under the plain radiography section above; the uninvolved side is shown for comparison.
Close-up MRI of the same distal femoral osteosarcoma as shown in image above, and in images shown under the plain radiography section above.

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Author

Timothy P Cripe, MD, PhD, FAAP Chief, Division of Hematology/Oncology/BMT, Gordon Teter Endowed Chair in Pediatric Cancer, Nationwide Children's Hospital; Professor of Pediatrics, Ohio State University College of Medicine

Timothy P Cripe, MD, PhD, FAAP is a member of the following medical societies: American Academy of Pediatrics, American Association for the Advancement of Science, American Association for Cancer Research, American Pediatric Society, American Society of Gene and Cell Therapy, American Society of Pediatric Hematology/Oncology, Connective Tissue Oncology Society, Society for Pediatric Research, Children's Oncology Group

Disclosure: Nothing to disclose.

Coauthor(s)

Ryan D Roberts, MD, PhD Assistant Professor, Principal Investigator, Center for Childhood Cancer and Blood Disorders, The Research Institute at Nationwide Children’s Hospital, James Comprehensive Cancer Center, Assistant Professor, Attending Physician, Pediatric Academic Associates, Division of Pediatric Hematology, Oncology, and BMT, Nationwide Children’s Hospital, Department of Pediatrics and James Comprehensive Cancer Center, Ohio State University College of Medicine

Ryan D Roberts, MD, PhD is a member of the following medical societies: American Association for Cancer Research, American Association for the Advancement of Science, American Society of Pediatric Hematology/Oncology, Children's Oncology Group, Connective Tissue Oncology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Steven K Bergstrom, MD Department of Pediatrics, Division of Hematology-Oncology, Kaiser Permanente Medical Center of Oakland

Steven K Bergstrom, MD is a member of the following medical societies: Alpha Omega Alpha, Children's Oncology Group, American Society of Clinical Oncology, International Society for Experimental Hematology, American Society of Hematology, American Society of Pediatric Hematology/Oncology

Disclosure: Nothing to disclose.

Chief Editor

Max J Coppes, MD, PhD, MBA Executive Vice President, Chief Medical and Academic Officer, Renown Heath

Max J Coppes, MD, PhD, MBA is a member of the following medical societies: American College of Healthcare Executives, American Society of Pediatric Hematology/Oncology, Society for Pediatric Research

Disclosure: Nothing to disclose.

Acknowledgements

Samuel Gross, MD Professor Emeritus, Department of Pediatrics, University of Florida College of Medicine; Clinical Professor, Department of Pediatrics, University of North Carolina at Chapel Hill School of Medicine; Adjunct Professor, Department of Pediatrics, Duke University School of Medicine

Samuel Gross, MD is a member of the following medical societies: American Association for Cancer Research, American Society for Blood and Marrow Transplantation, American Society of Clinical Oncology, American Society of Hematology, and Society for Pediatric Research

Disclosure: Nothing to disclose.